Tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms: a nationwide registry study.

BACKGROUND: Antiplatelet therapy, where regimens are tailored based on platelet function testing, has been introduced into neurointerventional surgery. This nationwide registry study evaluated the effect and safety of tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms compared with conventional therapy using a standard regimen. METHODS: This study enrolled 1686 patients in 44 participating centers who received stent assisted coiling for unruptured aneurysms between January 1, 2019 and December 31, 2019. The standard regimen (aspirin and clopidogrel) was used for all patients in the conventional group (924, 19 centers). The regimen was selected based on platelet function testing (standard regimen for clopidogrel responders; adding cilostazol or replacing clopidogrel with other thienopyridines (ticlopidine, prasugrel, or ticagrelor) for clopidogrel non-responders) in the tailored group (762, 25 centers). The primary outcome was thromboembolic events. Secondary outcomes were bleeding and poor outcomes (increase in modified Rankin Scale score). Outcomes within 30 days after coiling were compared using logistic regression analysis. RESULTS: The thromboembolic event rate was lower in the tailored group than in the conventional group (30/762 (3.9%) vs 63/924 (6.8%), adjusted OR 0.560, 95% CI 0.359 to 0.875, P=0.001). The bleeding event rate was not different between the study groups (62/762 (8.1%) vs 73/924 (7.9%), adjusted OR 0.790, 95% CI 0.469 to 1.331, P=0.376). Poor outcomes were less frequent in the tailored group (12/762 (1.6%) vs 34 (3.7%), adjusted OR 0.252, 95% CI 0.112 to 0.568, P=0.001). CONCLUSION: Tailored antiplatelet therapy in stent assisted coiling for unruptured aneurysms reduced thromboembolic events and poor outcomes without increasing bleeding.

Anatomical predictors of difficult left internal carotid artery navigation in transradial access for neurointervention.

OBJECTIVE: Transradial access (TRA) has received considerable attention in the field of neurointervention owing to its advantages over transfemoral access. However, the difficulty of left internal carotid artery (ICA) navigation under certain anatomical conditions of the aortic arch and its branches is a limitation of right TRA. In this study the authors aimed to investigate the anatomical predictors that impede navigation of the left ICA in right TRA. METHODS: From January to October 2020, 640 patients underwent transradial angiography at a single institute. Among them, 263 consecutive patients who were evaluated by contrast-enhanced MRA before transradial angiography were included in the study and assigned to success or failure groups according to whether left ICA navigation was possible or not. Several anatomical predictors were investigated to evaluate the correlation of the success of left ICA navigation in right TRA. RESULTS: A higher grade of the aortic arch type (type I vs type III: OR 6.323, p = 0.0171), higher height of the right subclavian artery (OR 1.071, p = 0.0068), narrower turnoff angle of the left common carotid artery (CCA) (OR 0.953, p = 0.0017), wider distance between the innominate artery and the left CCA (OR 1.784, p < 0.0001), steeper angulation of the right subclavian artery (tortuous vs kinking: OR 6.323, p = 0.0066), and steeper angulation of the left CCA (normal vs tortuous: OR 7.453, p = 0.0087; normal vs kinking: OR 51.65, p < 0.0001) were significantly associated with successful navigation of the left ICA. The cutoff value of the height of the right subclavian artery, distance between the innominate artery and the left CCA, turnoff angle of the left CCA, and diameter of the left CCA were 54.83 mm, 4.25 mm, 17°, and 6.05 mm, respectively. CONCLUSIONS: Successful left ICA navigation in right TRA was related to the specific vascular geometry of the aortic arch and its branches. Preprocedural evaluation of the anatomical predictors identified in this study may enhance the success rate of left ICA navigation in right TRA.

Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea.

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

Predictors of Significant Coronary Artery Disease in Patients with Cerebral Artery Atherosclerosis.

OBJECTIVE: There are few existing data on the status of coronary artery disease (CAD) in patients with atherosclerosis of the cerebral artery detected by brain imaging studies. We aimed to analyze the predictors of asymptomatic angiographically significant CAD detected by simultaneous cerebral and coronary angiography. METHODS: This retrospective cohort study screened data obtained between August 2009 and April 2019; 11,047 patients underwent cerebral angiography for atherosclerotic change (>50% stenosis or aneurysm) seen in brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) at a single center by endovascular neurosurgeon's decision. Of these, 700 patients including 622 patients who underwent simultaneous coronary and cerebral angiography and 78 patients who underwent coronary angiography within a month were enrolled. We investigated the characteristics and predictors of angiographically significant CAD (>50% stenosis). Furthermore, we also analyzed the major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, and stroke for 5 years. RESULTS: The frequency of significant CAD was 59% (413/700), the mean age was 68.9 ± 10.3 years, and 60.6% were male. During mean follow-up of 50 months, the MACCE rate of our whole cohort was significantly higher in the CAD group (21.5%) than in the non-CAD group (14.6%; hazard ratio 1.65, 95% CI 1.17-2.33, p value = 0.005). Considering that the embolic stroke is less associated with atherosclerotic change, our predictive model of significant CAD was made without embolic stroke (n = 599). In our multivariate model 2 including univariate <0.1, the independent predictors of significant CAD were male (OR 1.62, 95% CI 1.11-2.35, p = 0.012), diabetes mellitus (OR 1.81, 95% CI 1.22-2.68, p = 0.003), previous stroke (OR 1.63, 95% CI 1.02-2.60, p = 0.039), low ankle-brachial index (ABI; <0.9; OR 3.25, 95% CI 1.21-8.73, p = 0.019), left ventricular ejection fraction (EF) <50% on echocardiography (OR 2.82, 95% CI 1.25-6.35, p = 0.012), troponin I or T positive (OR 2.76, 95% CI 1.69-4.53, p < 0.001), and complex features on cerebral angiography (OR 2.73, 95% CI 1.78-4.19, p < 0.001). CONCLUSIONS: Accurate coronary evaluation by coronary angiography might be considered when patients with atherosclerotic cerebral artery detected on brain MRA or CTA planned cerebral angiography were male or have diabetes mellitus, previous stroke, low ABI (<0.9), left ventricular EF <50% on echocardiography, troponin I or T positivity, and complex features on cerebral angiography.

Headache Outcomes After Coil Embolization in Patients with Unruptured Intracranial Aneurysms: Do They Get Better or Worse? A Prospective Analysis.

BACKGROUND: To investigate the association between headache outcomes and coil embolization and to identify potential factors associated with different headache outcomes in patients with unruptured intracranial aneurysms (UIAs) after treatment with coil embolization. METHODS: A prospective study of patients with planned coil embolization for UIAs was conducted. The changes in headache patterns, headache-related disability, and depression were assessed before coil embolization and at 3 days and 2 and 6 weeks after coil embolization. All variables were analyzed to identify factors associated with different headache outcomes. RESULTS: Fifty-nine (72%) of 82 patients reported headaches before coil embolization. Of these, improvements in the severity of headaches were reported by 42 patients (71%). In addition to a significant reduction in headache severity, significant reductions in headache-related disability and depression scores also were observed. Demographic factors, aneurysmal characteristics, or procedural factors were not found to be significantly associated with improvement in the severity of headaches after coil embolization. In addition, the number of microemboli on diffusion-weighted imaging was not significantly associated with improvement of headaches after coil embolization. Twenty-three patients reported no headaches before coil embolization, and 3 (13%) patients reported new-onset headaches after coil embolization. All new-onset headaches were mild and dull in nature without combined symptoms in the temporal area. CONCLUSIONS: Our study suggested that regardless of headache characteristics, the aneurysm size (even those <5 mm in diameter), technique used (stent-assisted or not stent-assisted), and coil embolization of UIAs resulted in headache improvement in most patients with pretreatment headaches.

Usefulness and Stability of Intraoperative Digital Subtraction Angiography Using the Transradial Route in Arteriovenous Malformation Surgery.

BACKGROUND: Digital subtraction angiography is the gold standard to confirm complete removal of an arteriovenous malformation (AVM) nidus. However, the transfemoral approach requires specialized instrumentation and is cumbersome and difficult to perform with the patient in the prone or decubitus position. We report the use of intraoperative digital subtraction angiography (iDSA) with the transradial approach and examine its usefulness and safety. MATERIALS AND METHODS: We retrospectively reviewed clinical features, radiologic images, surgical findings, and iDSA findings of patients with AVM who underwent surgery for nidus removal. Transradial iDSA was performed within 30 minutes for patients who required angiographic confirmation after AVM resection. This procedure was simple with the radial arterial line for blood pressure monitoring used as digital subtraction angiography catheter access route. RESULTS: Transradial iDSA was performed in 23 patients. Twelve patients were not in the general supine position during neurosurgery; 7 patients were operated on in prone position, and 5 patients were operated on in the park bench position. Remnant nidus was identified by iDSA in 2 patients, and additional measures were required. CONCLUSIONS: Intraoperative cerebral angiography during surgery for cerebral AVM could be performed safely via the transradial approach. This approach showed several merits in terms of easy access; no extra requirements, such as preoperative sheath implantation, anticoagulation during the surgery, or a radiolucent table; and usefulness in any surgical position. Further studies using this approach and comparison with the transfemoral approach are necessary.

Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research. The aim of this report is to update pathologists, clinicians and researchers on TIL assessment in both the post-neoadjuvant residual disease and the ductal carcinoma in situ settings. The International Immuno-Oncology Working Group proposes a method for assessing TILs in these settings, based on the previously published International Guidelines on TIL Assessment in Breast Cancer. In this regard, these recommendations represent a consensus guidance for pathologists, aimed to achieve the highest possible consistency among future studies.

Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research.

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors.

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

Clinical Results of the Intra-Arterial Thrombolysis with Stent Retriever Device Weather Perfusion Diffusion Mismatching and Intravenous Tissue Plasminogen Activator Administration.

OBJECTIVE: Intraarterial thrombolysis (IA-Tx) with stent retriever is accepted as an additional treatment for selected patients and the clinical benefit is well reported. Each intravenous tissue plasminogen activator administration (IV-tPA) and perfusion diffusion mismatching (P/D-mismatching) is well known the beneficial effects for recanalization and clinical outcomes. In this report, authors analyzed the clinical outcomes of additional IA-Tx with retrieval stent device, according to the combined IV-tPA and P/D-mismatching or not. METHODS: Eighty-one treated IA-Tx with the Solitaire stent retriever device, diagnosed as anterior circulation larger vessel occlusion were included in this study. Computed tomography-angiography (CTA) was done as an initial diagnostic image and acute stroke magnetic resonance image (MRI) followed after the IV-tPA. Forty-two patients were in the tPA group and 39 patients were in the non-tPA group. Recanalization rate, clinically significant hemorrhagic (sICH) and clinical outcomes were recorded according to the IV-tPA and P/D-mismatching. RESULTS: Recanalization rate was 81.0% in IV-tPA group, and it was 69.2% in non-tPA group (p = 0.017). While sICH were 19.9% and 25.6%, respectively (p = 0.328). Neurologic outcomes did not influence by IV-tPA administration or not. But according to the P/D-mismatching, the recanalization rate and sICH were 91.9% and 16.7% in the mismatched group and 46.7% and 46.7% in the matched group (p = 0.008 and p = 0.019, respectively). CONCLUSION: For patients treated with IA-Tx with retrieval stent, IV-tPA infusion does not influence on the sICH, recanalization rate and neurologic outcomes. But P/D-mismatching was correlated well with sICH, recanalization rate and clinical outcomes.

Clinical Utility of Angiographic CT with a Flat-detector Angiographic System during Endovascular Procedure.

OBJECTIVE: We evaluated the feasibility of angiographic computed tomography (ACT) for visualizing stent material in patients who underwent intracranial or extracranial stent placement to treat atherosclerotic lesions or stent assisted coil embolization. MATERIALS AND METHODS: We performed intrarterial and intravenous ACT on biplane angiography system equipped with flat panel detectors (Axiom Arits dBA; Siemens Medical Solutions, Forchheim, Germany). Vistipaque 320 was injected for contrast medium, total 150 mL at flow rate of 5 mL/s through artery and 77 mL at flow rate of 3.5 mL/s through vein. RESULTS: ACT is a new imaging modality that provides a clear visualization of stent strut. CONCLUSION: Therefore this new application has potential to become the noninvasive option for follow-up after endovascular surgery using stents.

Trans-radial Carotid Artery Stenting in a Patient with Abdominal Aortic Occlusion.

We report transradial access (TRA) for emergency carotid artery stenting (CAS) as a useful alternative when the femoral artery cannot be accessed. A 63-year-old man arrived at our emergency room 30 minutes after left hemiplegia and loss of consciousness. Brain computed tomography (CT) anigograpy showed occlusion of the right interntal carotid artery (ICA) and CT perfusion revealed delayed time-to-peak in the territory of the middle cerebral artery. For, endovascular treatment, trans-femoral access (TFA) was attempted but failed due to occlusion of the abdominal aorta. So, we changed access route via radial artery and confirmed proximal ICA dissection. CAS was attempted via TRA and it was successfully performed. Final angiography showed recanalization of ICA and patient was clinically improved.

Treatment of the Superior Sagittal Sinus Thrombosis with the Mechanical Thrombectomy Using Stent-Retriever Device.

Cerebral venous sinus thrombosisis an uncommon entity and its clinical presentations are highly variable. We present the case of superior sagittal sinus thrombosis. Although it was medical refractory, successfully treated with mechanical thrombectomy using the Solitaire FR device. A 27-year-old man who presented with venous infarction accompanied by petechial hemorrhage secondary to the superior sagittal sinus (SSS) thrombosis. Due to rapid deterioration despite of anticoagulation therapy, the patient was taken for endovascular treatment. We deployed the Solitaire FR device (4×20 mm) in the anterior portion of the thrombosed SSS, and it was left for ten minutes before the retraction. Thus, we removed a small amount of thrombus. But the sinus remained occluded. We therefore performed the thrombectomy using the same methods using the Solitaire FR (6×20 mm). Thus, we were successful in removing larger clots. Our case highlights not only that the mechanical thrombectomy using the Solitaire FR is effective in achieving revascularization both rapidly and efficiently available, but also that it might be another option in patients with cerebral venous sinus thrombosis who concurrently had rapid clinical deterioration with devastating consequences.

Perfusion-Weighted MRI Parameters for Prediction of Early Progressive Infarction in Middle Cerebral Artery Occlusion.

OBJECTIVE: Early progressive infarction (EPI) is frequently observed and related to poor functional outcome in patients with middle cerebral artery (MCA) infarction caused by MCA occlusion. We evaluated the perfusion parameters of magnetic resonance imaging (MRI) as a predictor of EPI. METHODS: We retrospectively analyzed patients with acute MCA territory infarction caused by MCA occlusion. EPI was defined as a National Institutes of Health Stroke Scale increment ≥2 points during 24 hours despite receiving standard treatment. Regional parameter ratios, such as cerebral blood flow and volume (rCBV) ratio (ipsilateral value/contralateral value) on perfusion MRI were analyzed to investigate the association with EPI. RESULTS: Sixty-four patients were enrolled in total. EPI was present in 18 (28%) subjects and all EPI occurred within 3 days after hospitalization. Diabetes mellitus, rCBV ratio and regional time to peak (rTTP) ratio showed statically significant differences in both groups. Multi-variate analysis indicated that history of diabetes mellitus [odds ratio (OR), 6.13; 95% confidence interval (CI), 1.55-24.24] and a low rCBV ratio (rCBV, <0.85; OR, 6.57; 95% CI, 1.4-30.27) was significantly correlated with EPI. CONCLUSION: The incidence of EPI is considerable in patients with acute MCA territory infarction caused by MCA occlusion. We suggest that rCBV ratio is a useful neuro-imaging parameter to predict EPI.

Pipeline Embolization Device for Large/Giant or Fusiform Aneurysms: An Initial Multi-Center Experience in Korea.

PURPOSE: The purpose of this study was to assess the safety and early outcomes of the Pipeline device for large/giant or fusiform aneurysms. MATERIALS AND METHODS: The Pipeline was implanted in a total of 45 patients (mean age, 58 years; M:F=10:35) with 47 large/giant or fusiform aneurysms. We retrospectively evaluated the characteristics of the treated aneurysms, the periprocedural events, morbidity and mortality, and the early outcomes after Pipeline implantation. RESULTS: The aneurysms were located in the internal carotid artery (ICA) cavernous segment (n=25), ICA intradural segment (n=11), vertebrobasilar trunk (n=8), and middle cerebral artery (n=3). Procedure-related events occurred in 18 cases, consisting of incomplete expansion (n=8), shortening-migration (n=5), transient occlusion of a jailed branch (n=3), and in-stent thrombosis (n=2). Treatment-related morbidity occurred in two patients, but without mortality. Both patients had modified Rankin scale (mRS) scores of 2, but had an improved mRS score of 0 at 1-month follow-up. Of the 19 patients presenting with mass effect, 16 improved but three showed no changes in their presenting symptoms. All patients had excellent outcomes (mRS, 0 or 1) during the follow-up period (median, 6 months; range, 2-30 months). Vascular imaging follow-up (n=31, 65.9%; median, 3 months, range, 1-25 months) showed complete or near occlusion of the aneurysm in 24 patients (77.4%) and decreased sac size in seven patients (22.6%). CONCLUSION: In this initial multicenter study in Korea, the Pipeline seemed to be safe and effective for large/giant or fusiform aneurysms. However, a learning period may be required to alleviate device-related events.

Risk Factors for Early Hemorrhagic Progression after Traumatic Brain Injury: A Focus on Lipid Profile.

The purpose of this study was to identify the risk factors related to the hemorrhagic progression (HP) of brain contusion in patients after traumatic brain injury (TBI). Recently, many studies have reported abnormal lipid levels associated with hemorrhagic stroke. Unlike hemorrhage stroke, however, the lipid profiles in patients with TBI have not been examined. Therefore, we evaluated the risk factors of HP in patients with TBI and focused on lipid profiles. Fifty-six patients with TBI with mild to moderate injuries (Glasgow Coma Scale ≥9) who initially did not need surgical intervention were enrolled in this study. Patients underwent repeated computed tomography (CT) scans at 4 h and 24 h after injury. Magnetic resonance imaging (MRI) was performed 7 days after the initial injury. In each noncontrast CT scan, the hemorrhage volume was quantified using the ABC/2 technique. Clinical features, previous medical history, initial CT, and microbleeding on follow-up MRI were analyzed retrospectively. There were 31 (55%) patients in whom significant HP developed (volume >30%). Current smoking (p=0.034), higher initial systolic blood pressure (p=0.035), and lower triglyceride levels (p=0.039) were significantly associated with HP. Current smoking and a triglyceride (TG) level <150 mg/dL were the only statistically significant predictors of HP in the multivariate analysis (p=0.019, p=0.021, respectively). HP with TBI is common in patients who currently smoke and have lower TG levels (150 mg/dL). These patients should be monitored closely, and surgery may be considered before deterioration occurs.

Intrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant trastuzumab in the NSABP B-31 trial.

PURPOSE: Considerable molecular heterogeneity exists among human epidermal growth factor receptor 2 (HER2) -positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, clinical neoadjuvant, and metastatic clinical trials suggested that PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31. PATIENTS AND METHODS: Expression data for 49 genes using the nCounter platform were used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (n = 671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease-free survival as the end point. RESULTS: Seven hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34 to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P = .009), respectively (interaction P = .64). CONCLUSION: Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting.

Decreased diaphragm excursion in stroke patients with dysphagia as assessed by M-mode sonography.

OBJECTIVE: To record diaphragm excursion via M-mode ultrasonography in stroke patients with dysphagia and determine whether they present reduced diaphragm excursion during voluntary cough compared with stroke patients without dysphagia and healthy subjects. DESIGN: Prospective cross-sectional study. SETTING: University rehabilitation hospital. PARTICIPANTS: Acute stroke patients with dysphagia (n=23), acute stroke patients without dysphagia (n=24), and healthy control participants (n=27) (N=74). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Diaphragm motions during quiet breathing, deep breathing, and voluntary coughing were recorded via ultrasonography using M-mode tracing (mm). Maximum inspiratory and expiratory pressures (cmH2O) and peak cough flow (L/min) during voluntary coughing were measured. RESULTS: The mean diaphragm movement (mm) of the hemiplegic side for all groups during quiet breathing, deep breathing, and voluntary coughing was 14.8±4.3, 17.6±4.8, and 20.9±3.7 (P<.001); 23.8±7.1, 32.7±10.6, and 44.7±10.3 (P<.001); and 16.8±4.8, 28.5±4.9, and 36.0±8.2 (P<.001), respectively. The differences were statistically significant. Differences were observed in the maximum inspiratory (P<.001) and expiratory (P<.001) pressures and peak cough flow (P=.027) among the 3 groups. Forward selection stepwise regression analysis, which was performed to determine variables that help predict diaphragm excursion during voluntary coughing, showed that the presence of dysphagia explained up to 60% (P<.001) of the hemiplegic diaphragm movement during voluntary coughing in patients with stroke. CONCLUSIONS: M-mode ultrasonography showed that stroke patients with dysphagia have decreased diaphragm excursion and compromised respiratory function during voluntary coughing.

Predictors of malignant brain edema in middle cerebral artery infarction observed on CT angiography.

Patients with middle cerebral artery (MCA) infarction accompanied by MCA occlusion with or without internal carotid artery (ICA) occlusion have a poor prognosis, as a result of brain cell damage caused by both the infarction and by space-occupying and life-threatening edema formation. Multiple treatments can reduce the likelihood of edema formation, but tend to show limited efficacy. Decompressive hemicraniectomy with duroplasty has been promising for improving functional outcomes and reducing mortality, particularly improved functional outcomes can be achieved with early decompressive surgery. Therefore, identifying patients at risk for developing fatal edema is important and should be performed as early as possible. Sixty-four patients diagnosed with major MCA infarction with MCA occlusion within 8 hours of symptom onset were retrospectively reviewed. Early clinical, laboratory, and computed tomography angiography (CTA) parameters were analyzed for malignant brain edema (MBE). Twenty of the 64 patients (31%) had MBE, and the clinical outcome was poor (3month modified Rankin Scale >2) in 95% of them. The National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomography Score, Clot Burden Score, and Collateral Score (CS) showed statically significant differences in both groups. Multivariable analyses adjusted for age and sex identified the independent predictors of MBE: NIHSS score >18 (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 1.2-16.0, p=0.023) and CS on CTA <2 (OR: 7.28, 95% CI: 1.7-30.3,p=0.006). Our results provide useful information for selecting patients in need of aggressive treatment such as decompressive surgery.